We have developed two distinctly different approaches for successfully transplanting bone marrow across the H-2 barrier in mice without the complication of GVH disease. The first approach involves selectively deleting lymphocytes with specific GVH reactivity from the donors' marrow by diverting the traffic of these cells elsewhere (Fed. Proc. 37: 591, 1978). The second involves using heterologous anti-lymphocyte sera (ALS) plus supralethal irradiation to condition the marrow recipients. With both approaches successful engraftment and the induction of hematopoietic chimerism was to a great extent dependent upon the dose of marrow transplanted. Chimeric mice almost invariably permanently sustained skin allografts of marrow donor haplotype whereas non-chimeric mice did not. When 1 X 10 to the 7th power C57BL/6 marrow was transplanted to supralethally irradited AKR mice, the long-term survivors that were chimeric did not develop spontaneous leukemia-lymphomas. Non-chimeric long-term survivors had a high incidence of leukemia-lymphomas, as did normal untreated mice. We plan to employ both approaches to use allogeneic bone marrow in combination with chemoradiotherapy to treat the spontaneous leukemia-lymphomas that arise in AKR and SJL mice. We also plan to use both approaches to transplant marrow across the major histocompatibility complex in mongrel dogs.